Haggai Hermesh

Association between obsessive-compulsive disorder and polymorphisms of genes encoding components of the serotonergic and dopaminergic pathways

Obsessive-compulsive disorder (OCD) is a severe and disabling anxiety disorder with a marked genetic contribution. Pharmacological data indicated involvement of the serotonergic and dopaminergic systems. We studied the association between OCD and six candidate genes encoding important components of the serotonergic and dopaminergic pathways in 75 biologically unrelated patients and 172 ethnically matched controls (Ashkenazi and non-Ashkenazi Jews). Polymorphisms in the following genes were studied: tryptophan hydroxylase (TPH), serotonin 2A receptor (HTR2A), serotonin 2C receptor (HTR2C), serotonin transporter (5-HTT), dopamine receptor D4 (DRD4), and dopamine transporter (DAT1). The genotypic and allelic distribution of all polymorphisms tested did not show statistically significant differences between patients and controls. Our results suggest that these polymorphisms do not play a major role in the genetic predisposition to OCD, although a minor contribution cannot be ruled out.

Rituals, stereotypy and compulsive behavior in animals and humans

From a survey of the behavior of animals in the wild, in captivity, under the influence of psychoactive drugs and in a model of obsessive-compulsive disorder (OCD), we identify that the behavioral repertoire invariably includes motor rituals, and that such rituals are performed at a few specific locations/objects in the environment with an orderly transition amongst locations/objects. The concept and parameters of this stable organization of rituals in time and space were used to analyze rituals of OCD patients, compared with control individuals performing the same actions (e.g. car locking). It was found that human rituals also converged to a few places/objects where repetitive acts were performed in a regular order, with the acts in OCD patients overlapping with those of control individuals. Across a very diverse range of animals and conditions, motor rituals are thus characterized by their close linkage to a few environmental locations and the repeated performance of relatively few acts. Such similarity in form may reflect a similarity in the mechanisms that control motor rituals in both animals and humans.

Clinical characteristics of schizophrenia associated with velo-cardio-facial syndrome

Velo-cardio-facial syndrome (VCFS) is caused by a microdeletion in the long arm of chromosome 22 and is associated with an increased frequency of schizophrenia and bipolar mood disorder. The purpose of this study was to investigate the genetic, physical, developmental and psychiatric features of schizophrenic patients with VCFS microdeletion. It describes the clinical findings in four schizophrenic inpatients with the characteristic chromosomal deletion. The four patients displayed delayed motor development, language deficits, learning disabilities, mental retardation, early age of onset, chronic and disabling course of illness and poor response to classical neuroleptic drugs and electroconvulsive therapy. Two patients benefited from treatment with clozapine. We suggest that schizophrenic patients with a history of delayed motor development, early onset of the disorder, history of learning disability, mental retardation, congenital cardiac anomalies and/or hypernasal speech should be screened for the velo-cardio-facial syndrome deletion. The implications of this study for psychiatric phenotype, nosology, disease mechanism, and possible new treatments in the future are discussed.

Functional impairment in social anxiety disorder

The present study examined functional impairment among treatment seekers with social anxiety disorder (SAD). We investigated the effects of diagnostic subtypes of SAD and comorbidity with mood and anxiety disorders on impairment. In addition, we used cluster analysis procedures to empirically identify subgroups of individuals with distinct patterns of impairment. Participants were 216 treatment-seeking individuals with SAD. Clinical interviews were undertaken to determine diagnoses of anxiety disorders and major depressive disorder, and a battery of self-report measures was administered to index symptoms of social anxiety, depression and extent of impairment. Results indicated that individuals with the generalized subtype of SAD had greater impairment in all three life domains compared to individuals with the nongeneralized subtype. Comorbidity with mood disorders was associated with greater impairment than SAD alone, but comorbidity with anxiety disorders was not. Four distinct impairment profiles emerged from the cluster analysis: primary work/studies impairment, primary social life impairment, both work/studies and social impairment, and impairment in all domains. Findings from this study suggest that SAD is associated with substantial impairment across multiple domains, and that individuals with SAD present diverse impairment profiles. These profiles may inform subtyping of the disorder as well as therapeutic interventions.

Comparative neuropsychology of adult obsessive‐compulsive disorder and attention deficit/hyperactivity disorder: Implications for a novel executive overload model of OCD

Research implicates frontostriatal pathophysiology in both attention deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Nevertheless, ADHD is characterized with frontostriatal hypoactivity and OCD with hyperactivity. Furthermore, both disorders seem to lie on opposite ends of a clinical impulsive-compulsive continuum. While never having directly been compared, and despite these differences, OCD and ADHD appear to share similar neuropsychological impairments especially in executive functions. This study aimed at comparing adults with OCD and adults with ADHD on neuropsychological measures and behavioural impulsivity and OC measures. Thirty OCD, 30 ADHD, and 30 matched healthy control (HC) participants were administered a comprehensive neuropsychological battery and completed several questionnaires. The groups were compared on all neuropsychological and clinical measures and correlations between neuropsychological and clinical symptoms were computed. The ADHD and OCD groups performed more poorly than HC on all neuropsychological domains and most domain subtests. The ADHD group reported significantly higher impulsivity than the OCD group. OCD patients did not differ from HC on behavioural impulsivity. A unique dissociation was found between impulsivity and response inhibition where both clinical groups showed similar response inhibition deficit, but differed significantly on impulsivity. Moreover, a negative association between OC symptoms and response inhibition and a bias in self-perception of impulsivity was found only in the OCD group. We propose an executive overload model of OCD that views neuropsychological impairments in OCD as an epiphenomenon, according to which continuous attempts to control automatic processes are associated with obsessive thoughts overflow that causes an overload on the executive system.

Realism of confidence in obsessive-compulsive checkers.

The study examined whether obsessive-compulsive (OC) checkers have reduced confidence in their knowledge. OC checkers were compared with panic disorder (PD) patients and nonpatient controls using a calibration-of-knowledge procedure. Participants completed a general knowledge questionnaire, rated their confidence in each answer, and estimated the total number of correct answers. These responses were converted to 2 measures of confidence relative to performance--over/underconfidence and over/underestimation. OC checkers had lower scores than nonpatients did on both measures, whereas the PD patients did not differ from either group. For the OC checkers, relative confidence was inversely related to the severity of obsessions. The authors speculate that confidence may depend on a confirmation bias in testing hypotheses and that the reduced confidence in OC checkers may reflect a disconfirmation bias in this population.

Bruxism secondary to antipsychotic drug exposure : A positive response to propranolol

We present two cases of acute nocturnal bruxism occurring as an early side effect of antipsychotic drug treatment. The development of bruxism was coupled with the appearance of neuroleptic-induced akathisia. Both complications were relieved after the beta-adrenergic blocker propranolol was added, suggesting the involvement of the adrenergic and serotonergic central nervous systems, besides the dopaminergic system, in the pathogenesis of bruxism. The positive response of iatrogenic bruxism to propranolol implies that propranolol also deserves a trial for the treatment of noniatrogenic nocturnal bruxism.

Neuroimaging communality between schizophrenia and obsessive compulsive disorder: a putative basis for schizo-obsessive disorder?

Summary Four major brain regions have been repeatedly implicated in the pathophysiology of obsessive compulsive disorder (OCD) in in vivo neuroimaging studies: the caudate nucleus, the orbitofrontal cortex, the anterior cingulate gyrus and the mediodorsal thalamic nucleus. The present review describes the neuroimaging studies on schizophrenia, pertaining to these brain regions. Our working hypothesis is that such common brain regions, if dysfunctional in schizophrenic patients, would be candidates for a neural network subserving the newly emerging syndrome of schizo-obsessive disorder. Findings, though, are controversial. We conclude that further studies, aimed at specific monitoring of these brain regions, in patients suffering from the schizo-obsessive syndrome are warranted.

Obsessive-compulsive disorder: a disorder of pessimal (non-functional) motor behavior

Objective:  To determine whether in addition to repetitiveness, the motor rituals of patients with obsessive–compulsive disorder (OCD) involve reduced functionality due to numerous and measurable acts that are irrelevant and unnecessary for task completion.

Impaired procedural learning in obsessive-compulsive disorder and Parkinson's disease, but not in major depressive disorder.

The striatum has been consistently implicated in the pathophysiology of obsessive-compulsive disorder (OCD), yet, studies assessing the performance of OCD patients in procedural learning tasks, assumed to rely on the intact functioning of the striatum, have yielded inconsistent results. Recently, Rauch et al. [Rauch SL, Savage CR, Alpert NM, Dougherty D, Kendrick A, Curran T, et al. Probing striatal function in obsessive-compulsive disorder: a PET study of implicit sequence learning. J Neuropsychiatry Clin Neurosci 1997;9:568-73] have obtained evidence suggesting that seemingly intact performance of OCD patients in such tasks may be achieved by recruiting systems which in normal subjects are reserved for explicit or declarative, rather than implicit or procedural, processing. The present study assessed procedural learning in OCD patients using a card betting task in which explicit processing impairs, rather than assists, acquisition. In addition, we tested a group of Parkinsons disease (PD) patients, in order to better establish the dependence of the task on procedural learning, and a group of major depressive disorder (MDD) patients, in order to test the possibility that impaired learning in the card betting task may be a result of concurrent depression. The majority of OCD (15/18) and PD patients (14/16) did not acquire the task, whereas MDD patients acquired the task similarly to normal control subjects. These results demonstrate that OCD patients are impaired on a procedural learning task in which explicit processing impairs acquisition. Two different interpretations are suggested: that the striatal system is dysfunctional in OCD, or that inappropriate explicit processing in OCD interferes with the functioning of the striatal system.